Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in triple negative breast cancer

Area of Science:

• Molecular Oncology
• Cancer Therapeutics
• Non-coding RNA Biology

Background:

• Breast cancer is a leading cause of cancer death in women globally.
• Long non-coding RNAs (lncRNAs) play critical roles in cancer progression, acting as oncogenes or tumor suppressors.
• The specific role of taurine upregulated gene (TUG1) in triple-negative breast cancer (TNBC) chemotherapy sensitivity remains unelucidated.

Purpose of the Study:

• To investigate the role of TUG1 in mediating chemotherapy sensitivity in triple-negative breast cancer (TNBC).
• To explore the molecular mechanisms underlying TUG1's function in TNBC, including its interaction with microRNAs and signaling pathways.
• To assess the correlation between TUG1 expression and patient prognosis in breast cancer.

Main Methods:

• Quantitative analysis of TUG1 expression in TNBC tumor tissues and cell lines compared to normal tissues and other breast cancer subtypes.
• Functional assays involving TUG1 overexpression and silencing in TNBC cell lines (MDA-MB-231, BT549) to assess cisplatin-induced effects on cell growth and proliferation.
• Dual-luciferase reporter assays to confirm the interaction between TUG1 and miR-197, and to validate NLK as a target gene of miR-197.
• Analysis of the WNT signaling pathway and correlation of TUG1 expression with patient prognosis using TCGA database.

Main Results:

• TUG1 expression was significantly decreased in TNBC tumor tissues and cell lines.
• Overexpression of TUG1 enhanced cisplatin-induced cell growth arrest and proliferation inhibition in TNBC cells, while TUG1 silencing reduced these effects.
• TUG1 was found to negatively regulate miR-197, and NLK was identified as a downstream target of miR-197.
• TUG1 inactivated the WNT signaling pathway via the miR-197/NLK axis, thereby increasing TNBC chemotherapy sensitivity.
• Higher TUG1 expression correlated with better prognosis in breast cancer patients.

Conclusions:

• TUG1 plays a crucial role in enhancing chemotherapy sensitivity in triple-negative breast cancer.
• The TUG1/miR-197/NLK axis regulates the WNT signaling pathway, influencing TNBC chemosensitivity.
• TUG1 serves as a potential prognostic biomarker and therapeutic target for improving breast cancer treatment outcomes.